SYNERGISTIC EFFECTS OF COEXPRESSION OF THE TH1 CYTOKINES IL-2 AND IFN-GAMMA ON GENERATION OF MURINE TUMOR-REACTIVE CYTOTOXIC-CELLS

While the effect of cytokines on the generation of tumor-reactive cyto toxic cells has been a topic of active investigation, the effect of ph ysiological cytokine combinations has not been determined. We have inv estigated the effect of co-expression of IL-2 and IFN-gamma on the gen eration of cytotoxic cells against the murine line 1 tumor in vivo. Th ese cytokines were selected because they are normally produced in conc ert by a subset of T-helper cells called T-helper 1 (Th1). We transfec ted the line 1 murine carcinoma with cDNA for IL-2 and IFN-gamma, alon e or combined. IFN-gamma alone does not elicit rejection of the transf ectant, but IL-2 increases the tumorigenic dose by 10,000-fold above t he parental cells. Go-expression of IFN-gamma and IL-2 increases this rejection to at least 100,000-fold above parental line 1. Unlike IL-2 transfectants, tumor cells expressing both IFN-gamma and IL-2 can also elicit rejection of admired parental tumor cells. Finally, the IFN-ga mma/IL-2 transfectants are more effective at generating memory cells t hat are cytolytic for the parental tumor. Our results show that synerg istic interactions of Th1 cytokines can remarkably enhance the cytotox ic response to tumors. (C) 1995 Wiley-Liss, Inc.